SK167499A3 - A delivery system for an oral care substance using a strip of material having low flexural stiffness - Google Patents

Abstract

The invention relates to a delivery system for delivering a phosphate to a surface of the oral cavity, the delivery system comprising a strip of flexible material and an oral care substance applied to the strip of material, the oral care substabnce comprising the phosphate such that when the delivery system is placed on the oral surface, the substance contacts the surface providing the phosphate onto the surface.

Description

Oral Care Substance Delivery System that uses a strip of low rigidity material to bend

Technical field

This patent application is in part a continuation of the previously filed patent application 08 / 870,664, filed on June 6, 1997.

The present invention relates to a system of administering a substance or composition for oral care (drug substance) to the surface of the oral cavity including teeth, gums and mucous tissues, said substance being protected from erosion and oral saliva response. the cavity for a period of time sufficient to provide a therapeutic result. In particular, the present invention relates to a disposable delivery system that is cheap and non-intrusive.

BACKGROUND OF THE INVENTION

The customer needs a cheap oral delivery system that is convenient to wear and that can deliver a sufficient amount of the active ingredients of the substance to the oral cavity quickly. In addition, a delivery system is required that does not require the user to complicate the positioning of the system, which should assure the user that good contact has been ensured for optimal administration. Further, the active means of administration is not required to be too bulky and to allow the user to participate in the discussion without apparent restriction. Further, a composition with a high uptake capability is required to protect the substance from erosion caused by contact with other oral cavity surfaces or saliva.

2. Summary of the Invention

In practicing the present invention, a user applies a strip of material to the respective surface of the oral cavity. The side of the strip of material that faces the oral cavity surface is or is coated with a substance intended for oral care, or the oral cavity surface is coated and covered with a strip of material. In any case, the substance is viscous, e.g. a gel that can even provide dosing of the active agent and stickiness of contact between the oral cavity surface and the strip of material, thereby ensuring the placement and residence of the substance at the intended site. The strip may have a shape and size large enough to cover the surface of the oral cavity, for example, the entire surface of the upper and lower gums or adjacent teeth. By being made of a soft and adaptable material, the strip can come into contact with the gums without causing irritation. The strip of material adheres easily to the surface of the oral cavity by lightly pressing. The strip of material adapts readily to the oral cavity surface when the delivery system is introduced, without permanent deformation. The strip of material can easily peel off from the surface of the oral cavity. Successful treatment requires the use of a new strip of material each time.

The substance used forms a thin coating which contains a small amount of the substance as opposed to the substance administered by a conventional device. By administering a small amount of the substance, there is no unnecessary loss of said substance, for example by unwanted swallowing, while at the same time reducing the risk of irritation of the sensitive tissue by the substance. The strip of material and said substance may be transparent so that they are hardly visible in use, which is particularly important when applied to anterior teeth and adjacent gum tissues.

The delivery system also includes an oral care substance. ¹¹ which is applied to the strip of material such that when the strip is placed on the oral cavity surface, said substance contacts the surface and imparts to it an active substance. The substance also provides a connection between the strip of material and the surface of the oral cavity and thus keeps the system in place, allowing sufficient time for the active agent to operate on the surface of the oral cavity. It is preferred that the substance be used in the form of a gel capable of forming a uniform coating on the strip of material.

Another aspect of the present invention provides a method of administering said substance to a surface of the oral cavity by applying the substance to a shape-adaptive strip of material. An alternative step may be to directly apply the substance to the surface and immediately overlay the substance with a strip of material. Both possible methods ensure the transfer of the active agent to the oral cavity surface and the connection between the strip of material and the surface, thereby ensuring that the dispensing system is positioned at the intended location to allow sufficient time for the active agent to function properly on the surface.

Overview of the figures in the drawing

Although the specification of the present invention corresponds to the claims that emphasize and clearly claim the present invention, it will be understood that the present invention will be more readily understood from the following description and the accompanying drawings, in which: FIG. 1 is a perspective view of a flat strip of material with rounded corners; FIG. 2 is a perspective view of an embodiment of the flat ribbon of FIG. 1, which is coated with a drug substance for the treatment of teeth, FIG. 3 is a cross-sectional view of the line taken along line 3-3 of FIG. 2, by using a flat strip of material having a thickness less than the thickness of the deposited substance; FIG. Fig. 4 is a cross-sectional view showing an alternative embodiment of the present invention, showing shallow buckets in a strip of material that serves as a reservoir of substance applied to the surface of the strip for oral care; 5 shows a cross-sectional view of an alternative embodiment of applying a substance to the treated teeth by means of a strip of material according to the invention which has conformed to the shape and adhered to the teeth by means of a medicinal substance positioned between the teeth;

1 'with a strip of material, FIG. 6 is a cross-sectional view of the tooth and surrounding soft tissue taken along line 6-6 of FIG. 5 and illustrates a strip of material according to the invention adhesively bonded to the teeth by means of a drug substance disposed between the teeth and the strip of material; FIG. 7 is a cross-section similar to FIG. 5 showing a strip of material according to the present invention and surrounding soft tissue, wherein the strip is adhesively attached to both sides of the teeth by means of a drug substance positioned between the teeth and the strip of material; 8 is a cross-sectional view taken along line 8-8 of FIG. 7

Fig. 4 shows a strip of material according to the present invention wherein said strip is attached to both sides of the teeth as well as to the surrounding soft tissue by means of a drug substance positioned between the tooth and the strip of material; 9 is a perspective view of an alternative embodiment of the present invention in which the strip of material is coated with the drug substance of FIG. 2 for the treatment of teeth and further comprising a removable washer, FIG. 10 is a cross-sectional view of an alternative embodiment of the present invention taken along line 10-10 of FIG. 9 showing a removable pad attached to a strip of material by a drug substance applied to the strip of material.

DETAILED DESCRIPTION OF THE INVENTION

With reference to the accompanying drawings, and in particular to FIG. 1 and 2, in which the first embodiment of the present invention, denoted by the numeral 10, is shown, which embodiment is a delivery system for delivering a drug substance to the oral cavity surface. The delivery system 10 comprises a strip of rounded corner material 12 that is initially flat.

A drug substance 14 is applied to the strip of material 12. A homogeneous, uniform and continuous application of the drug substance to the strip of material 12 is preferred, as shown in FIG. 3. The drug substance 14 may be a laminate or separate layers of ingredients, an amorphous mixture of ingredients, separate strips or dots, or another sample of different ingredients, or a combination of these structures, comprising a continuous coating of the drug substance 14 applied along the longitudinal axis of a portion of the strip.

Fig. 4 shows an alternative embodiment of a strip of material 12 that includes shallow buckets 18. After the substance 14 has been applied to the respective side of the strip of material 12, it fills another

1, the drug substance shallow buckets 18, thus forming a reservoir of another drug substance 14.

In FIG. 5 and 6, the delivery system 24 of the present invention is shown applied to the tooth surface and to a plurality of adjacent teeth. A plurality of additional teeth 22 are embedded in the adjacent soft tissue 20. Adjacent soft tissue is defined herein by the soft tissue surfaces surrounding the dental structure and comprising: papilla, loose gum, gingival sulcus, interdental gum, gum structure on the lingual and cheek surfaces, including mucogingive and climate.

FIG. 5 and 6, the delivery system 24 is represented by a strip of material 12 and a drug substance 14 located on the side of the strip of material 12 facing the tooth 22. The drug substance 14 may be pre-applied to the strip or applied by the user of the delivery system. alternatively, the user applies the drug substance 14 directly to the teeth 22 and then overlaps it with a strip of material 12. In all cases, the strip of material 12 has such a thickness and bending stiffness that allows the strip to conform to the surfaces of the teeth 22 and adjacent soft tissue. The strip of elastic material has sufficient elasticity to form a surface contour, in which case the surface is adjacent teeth. The strip of material adapts easily to the tooth surfaces and the inter-fabric space of the teeth without causing permanent deformation. The delivery system is applied without applying more pressure.

Fig. 7 and 8 illustrate a delivery system 24 according to the present invention that is applied to both sides of adjacent teeth 22 and adjacent soft tissue 20. The delivery system 24 includes a strip of material 12 and a drug substance 14 that is located on the side of the strip of material 12 that faces the teeth 22.

Fig. 9 and 10 show an optional removable washer 27. The removable washer 27 is attached to the strip of material 12 by the drug substance 14. The drug substance 14 is deposited on the side of the strip of material 12 that faces the removable washer 27. This side is applied to the tooth surface as soon as is said removable pad removed.

Material strip

The strip of material serves as a protective barrier to the drug substance. The strip of material prevents leaching and / or erosion of the drug substance, which may be caused by the user's lips, tongue and> saliva. This allows the active substance present in the drug substance to act on the surface of the oral cavity for a period of time, i.e., a few minutes to several hours. The term "act on" is defined here as a change-producing activity. For example, if the drug substance is an anti-gum inflammation substance, it reduces and prevents bleeding and improves the healing of the gum tissue.

The strip of material may include polymers, natural and synthetic woven materials, nonwoven materials, film, paper, rubber, and a combination of said materials. The strip of material can

- be a single-layer material or laminate with more than one layer. Regardless of the number of layers, this strip of material is impermeable to water. The strip may be any type of polymer or a combination of polymers that meet the flexural rigidity requirements and are compatible with the drug substance. Suitable polymers may include, but are not limited to, polyethylene, ethylvinyl acetate, polyesters, ethylvinyl alcohol, and combinations thereof. Examples of polyesters include Mylar and fluoroplastics, for example Teflon, which is manufactured by Co. DuPont. The preferred material is polyethylene. The strip thickness of the material is generally less than 1 mm, preferably less than 0.05 mm, preferably from 0.001 to 0.03 mm. The polyethylene strip of the material has a thickness of less than 0.1 mm, preferably from 0.005 to 0.02 mm.

The strip of material requires a shape that is capable of covering the intended surface of the oral cavity. Preferably, the shape is rounded corners. Rounded corners are defined by not having sharp angles and points. In one example, the strip of material has a length of from 2 cm to 12 cm, preferably from 4 cm to 9 cm. The width of the strip of material also depends on the size of the area to cover. In one example, the width of the strip is from 0.5 cm to 4 cm, preferably from 1 cm to 2 cm.

The strip of material may include shallow buckets. Upon application of the drug substance to the strip of material, a portion of the substance fills the shallow buckets to form drug substance reservoirs. Shallow buckets give texture to the feed system. The film includes a grouping of shallow buckets. Shallow buckets are generally 0.4 mm in transverse direction and 0.1 mm deep. When the strip of material comprises shallow buckets and the drug substance is applied to the strip of varying thickness, the total thickness is less than 1 mm, preferably less than 0.5 mm.

The flexural stiffness as a function of the material property is a function of the combination of strip thickness, width, and modulus of material. This test is a method of measuring the stiffness of a polyolefin film and a method of layering. Determines the bending resistance of the sample using an extensometer attached to the end of the horizontal beam. The opposite end of the bundle pushes across the strip, part of which is forced into the vertical groove in the horizontal platform on which the sample rests. The micro-ammeter connected to the extensometer is calibrated in grams of bending force. The stiffness of the sample is read directly on the microamperimeter and is expressed as g / cm of the width of the sample strip. According to the invention, the strip of material has a bending stiffness of less than

-Ί 5 g / cm, measured on a Handle-O-Meter, Model # 211-300, available from R & Thwing-Albert Instrument Co. of, P A, Philadelphia, for the ASTM D2923-95 Test Method. Preferably, the strip of material has a flexural stiffness of less than 3 g / cm, preferably less than 2 g / cm, preferably about 0.1 g / cm. It is also preferred that the bending stiffness has a constant value and does not change during use. For example, the strip of material need not be hydrated in order to obtain flexural stiffness, with values within the stated range.

The relatively low stiffness of the strip of material makes it possible to cover the contours of the oral cavity surface with very little force. This means that the capability of conforming to the contour of the oral cavity is retained because there is very little residual force in the strip of material to return the strip to its original size, i.e. flat state, before being applied to the oral cavity surface. The elasticity of the material strip allows it to contact the soft tissue surface for a longer period of time and without irritation. The strip of material does not require the application of pressure when forming the strip on the oral cavity surface.

The strip of material is maintained on the surface of the oral cavity by adhesive bonding by the drug substance. The viscosity and generally the tackiness of the drug substance causes the strip of material to adhere to the surface of the oral cavity without slipping, which may be caused by frictional forces caused by the movement of lips, teeth, tongue and other movements of the oral cavity that rub against the strip of material. while talking or drinking, etc. However, the adhesion to the surface of the oral cavity is sufficiently low that the strip of material can be easily removed by the user simply peeling it off with a finger, nail or some soft swab. The delivery system is easily removed from the tooth surface without the use of any tools, chemical diluent, other chemical or excessive frictional force.

Chemical diluents contain organic diluents that often enter the mouth, e.g. i

alcohol and other safe diluents, for example water, which can dilute the gel present.

The force required to peel a strip of material from the surface of the oral cavity has a value of about 1 gram to 50 grams per strip of width of 1.5 cm (approximately 17 g / cm). The force required to peel the strip should be from 10 g to 40 g, preferably from 20 g to 30 g. The low force required has the advantage of being easy to handle by the user. The use of the small force required to adhere a strip of material with low bending stiffness is made possible by the non-aggressive nature of the drug substance. This means that the strip has a higher flexural stiffness

Requires the use of a more aggressive adhesive to prevent the strip of material from detaching from the contours of the oral cavity surface.

The strip of material can be made by many manufacturing processes, from films (thin materials) known in the art. The strip of polyethylene material can be made by blowing or casting. Other techniques include extrusion and generally other techniques that do not affect the bending stiffness of the resulting strip of material. The drug substance may be applied to the strip of material during the strip formation, for example by lamination.

Medicinal substances

The drug substance contains the active substance in an amount which, when applied directly, benefits the user without any damage to the oral cavity surface to which the active substance is applied. Examples of conditions for use of the active ingredients in the oral cavity will be given below, the use of said active ingredients being not limited to the appearance and structural changes of the teeth, whitening, bleaching, staining of teeth, calculus, caries prevention, bleeding and gum inflammation. , treatment of injured mucosa, various injuries, ulcers, aphthae, cold sores and dental abscesses.

The amount of drug substance used on the strip of material or on the surface of the oral cavity depends on the size and capacity of the material, the concentration of the active substance and the therapeutic intention. Generally less than 1 g of said substance is required. An amount of from 0.05 g to 0.5 g, preferably from 0.1 g to 0.4 g, is preferred. The amount of drug substance per cm ^{2 of} material is less than 0.2 g / cm ² , preferably from 0.005 to 0.1 g / cm ² .

The drug substance may be in the form of a viscous liquid, paste, gel, solution, and other suitable form which provides sufficient adhesion. Gel is preferred. Drugs l ¹ I

(The substance has a viscosity in the range of 200 to 1,000,000 cps at a low shear value (less than 1 / s). A value of from 100,000 to 800,000 cps, preferably from 400,000 to 600,000 cps is preferred.

Active substances

Suitable material for the active substances may be any material that is safe when used in the oral cavity, which provides changes in the oral health and

The particular state of oral cavity surfaces in contact with the drug substance. The level of the active ingredient according to the invention is about 0.01% to 40%, preferably from 0.1% to 20%, even more preferably from 0.5% to 10%, preferably from 1% to 7% by weight of the drug substance.

The pharmaceutical compositions or substances of the present invention may include many of the active ingredients already mentioned in the prior art. The following data is not a list of all possible active drug substances that can be used in the present invention.

1. Bleaching active substances

These active substances can be simultaneously the therapeutic substances according to the invention. Suitable bleaching agents are selected from the group consisting of iron chlorite peroxides, perborates, percarbonates, peroxyacids, and combinations thereof. Suitable peroxides are hydrogen peroxide, calcium peroxide, carbamide peroxide and mixtures thereof. Carbamide peroxide is preferred. Suitable iron chlorites are, for example, calcium chlorite, sodium chlorite and potassium chlorite. Further bleaching agents may be hypochloride and chlorine dioxide. The preferred chlorite is sodium chlorite.

2. Phosphates

Anti-tartar agents include phosphates. Phosphates include pyrophosphates, polyphosphates, polyphosphonates and mixtures thereof. Pyrophosphates are among the best known products used in dentistry. The pyrophosphate ions supplied to the teeth are derived from pyrophosphate salts. The pyrophosphate salt is present in the alloy used at present, comprises a divalent alkali metal pyrophosphate salts, and the alkali metal trojmocké · ^'1 pyrophosphate salts, and mixtures thereof. Disodium dihydrogen pyrophosphate (Na 2 H 2 P 2 O7), tetrasodium pyrophosphate (Na 4 P 2 O7), and tetrapotassium pyrophosphate (K4 P2 O ₇₎ and the dehydrated form of the hydrate are preferably used among the ingredients. Although all of the aforementioned polyphosphate salts may be used, tetrasodium pyrophosphate salt is preferred.

The pyrophosphate salts are described in greater detail in the Encyclopedia of Chemical Technology, Third Edition by Kirk & Othmer, Volume 17, Wiley-Interscience Publisher (1982), herein incorporated by reference. Other unpurified substances include pyrophosphates or

10 polyphosphates, disclosed in U.S. Patent 4,590,066, issued to Parran & Sakabb on May 20, 1986, the polyacrylates and polycarboxylates disclosed in U.S. Pat. No. 3,429,963, issued to Shedlovsky on February 25, 1969; No. 4,304,766, issued to Chang on December 8, 1981; No. 4,666,341, issued to Benedict & Sunberg on April 28, 1987, further include the polyepoxy succinates (polyepoxysuccinates) disclosed in U.S. Pat. No. 4,846,650 issued to Benedict, Bush and Sunbergt on July 11, 1989; ethylenediaminetetraacetic acid (ethylenediamine tetraacetic), disclosed in GB Patent 490,384, issued February 15, 1937; nitrilotriacetic acid (nitrilotriacetic); No. 3,668,154, issued to Widder & Briner on July 18, 1972, the polyphosphonates disclosed in U.S. Pat. No. 3,737, issued to Ploger, Schmidt-Dunker & Gloxhuber on October 26, 1976; No. 4,877,603 issued to Degenhardt & Kozikowski on October 31, 1989, all of said patents being incorporated herein by reference. Unpurified phosphates include potassium and sodium pyrophosphates, sodium tripolyphosphates, diphosphonates such as ethane-1 hydroxy-1, diphosphonate, 1-azacycloheftane-1,1-diphosphonate and linear diophosphonates, linear carboxylic acids and sodium zinc citrate.

Substances that could be used in place or in combination with pyrophosphate salts include such known materials as anionic polymers such as polyacrylates and copolymers of maleic anhydride or acid and methyl vinyl ether (e.g., Gantrez), such as those disclosed in the US U.S. Patent 4,627,977 issued to Gaffar et al., the conclusions of which are hereby incorporated by reference, polyamino propane sulfonic acid (AMPS), zinc citrate trihydrate, polyphosphates (tripolyphosphate, hexametaphosphate), diphosphonates (e.g. EHDP, AHP), polypeptides (e.g. polyaspartic and polyglutamine) and mixtures thereof.

3. Ionfluoride source

Sources of fluoride ions are known in the art of oral care as anti-antioxidants. Fluoride ions are included in many oral care compositions, such as toothpastes. Dental tooth patents include U.S. Pat. No. 3,538,230 issued to Pader et al. on Nov. 3, 1970, U.S. Pat. No. 3,689,637 issued to Pader et al. on Sep. 5, 1972, U.S. Pat. U.S. Patent 3,711,604 issued to Colodney et al. U.S. Patent 3,911,104 issued to Harrison on October 7, 1975;

11 Patent 3,935,306 issued to Roberts et al. on Jan. 27, 1976, U.S. Pat. No. 4,040,858 issued to Wason on August 9, 1977.

By applying fluoride ions to the enamel, the teeth are protected from tooth decay. A wide range of fluoride ion-containing materials can be used as the source of soluble fluoride in instant compositions. Suitable examples of fluoride-containing materials can be found in U.S. Pat. No. 3,535,421 issued to Briner et al. on October 20, 1970, U.S. Pat. No. 3,678,154 issued to Widder et al. on July 18, 1972. Both patents are incorporated herein by reference. Preferred fluoride ion sources include sodium fluoride, potassium fluoride and ammonia fluoride. Sodium fluoride is preferred. The instant composition provides about 50 ppm to 10,000 ppm, preferably about 100 to 3000 ppm, of ion fluoride in an aqueous solution that contacts the tooth surface when used in the mouth on a strip of material.

4. Antimicrobial agents

The antimicrobial agents may also be present in the compositions and substances for oral care of the present invention. Such substances may include, but are not limited to, tricosan, 5-chloro-2- (2,4 dichlorophenoxy) phenol, which is described in The Merck Index, 11th edition (1989) p. No. 1529 (accession number 9573 in US patent 3,506,720 and European patent application 0,251,591 filed by Beecham, PLC, published Jan. 7, 1988; chlorhexidine (Merck Index No. 2090); alexidine (Merck Index No. 222); hexetidine (Merck Index No. 4624) sanguinarine (Merck Index No 8320), benzalkomium chloride (Merck Index No 1066), salicilanilide (Merck Index No 8299), domifene bromide (Merck Index No 3411), cetylpyridinium chloride (CPC) (Merck Index No. 2024);

Tetradecylpyridinium chloride (TPC); N-tetradecyl-4-ethylpyridinium chloride (TDEPC); octenidine; octapinol and other piperidine derivatives; nicine preparations; zinc / tin ion substances; antibiotics, for example augmentin, amoxicillin, tetracycline, doxycycline, minocycline, and metronidazole; and the like and salts of the aforementioned antimicrobial anti-coating agents.

- 125. Anti-inflammatory substances

Anti-inflammatory agents may also be present in the compositions or substances used for oral care. Such agents may include, but are not limited to, non-steroidal anti-inflammatory agents or NSAIDs such as ketorolac, flurbiprofen, ibuprofen, naproxen, indomethacin, aspirin, ketoprofen, piroxicam, and meclofenamic acid. The use of NSAIDs, such as ketorolac, is claimed in U.S. Pat. No. 5,626,838, issued May 6, 1997, which is incorporated herein by reference. Disclosed herein are methods for the prevention and treatment of primary and recurring squamous cell carcinomas in the oral cavity or oral cavity of the larynx.

6. Nutrients

Nutrients can improve oral cavity conditions and can be incorporated into the composition or substance of the invention. Nutrients include minerals, vitamins, nutrients, administered orally and internally, and mixtures thereof.

Minerals that may be included in the composition of the invention may include calcium, phosphorus, fluoride, zinc, manganese, potassium, and mixtures thereof. These minerals are listed in "Drug Facts and Comparisons", Wolters Kluer, Company, St. Petersburg. Louis, Mo., 1997 p. 10-17. The document is given for comparison.

Vitamins may be used together with minerals or may be used alone. Vitamin C and D, thiamine, riboflavin, calcium pantothenate, niacin, folic acid, nicotinamide, pyridoxine, cyanocobalamin, para-aminobenzoic acid, bioflavonoids and mixtures thereof are used. These vitamins are listed in "Drug Facts and Comparisons," Wolters Kluer Company, St. Petersburg. Louis, Mo. 1997, p. 3-10. The document is given for comparison. Foods include amino acids, lipotropics, fish oil, and mixtures thereof, as set forth in "Drug Facts and Comparisons, Wolters Kluer Company, St. Louis, Mo. 1997, p. 54-54 e. The document is included for comparison. Amino acids include, but are not limited to, L-Tryptophan, L-Lysine, Methionine, Threonine, Levocarnitine, or L-Carnitine, and mixtures thereof. Lipotropic agents include, but are not limited to, choline, inositol, betaine, linoleic acid, and mixtures thereof. Fish oil contains a large amount of Omega-3 (N-3) poly unsaturated fatty acid, eicosapentanoic acid and decosahexanoic acid.

Nutrition, absorbed by the intestine, includes, but is not limited to, protein products, polymers, glucose, corn oil, medium chain triglycerides, as set forth in "Drug Facts and Comparisons", Wolters Kluer Company, St. Petersburg. Louis, Mo. 1997, p. 55-57.

I

7. Enzymes

The individual enzymes or combinations of compatible enzymes can be used as compositions or substances of the invention administered orally. Enzymes are biological catalysts of chemical reactions in living systems. The enzymes combined with the substrates in which they act form an intermediate enzyme-substrate complex. This complex is then converted into the reaction product and the released enzyme, which continues a particular enzymatic function.

Enzymes play an important role in cleaning the oral cavity. The protease disrupts the saliva proteins that are absorbed on the dental surface and form a coating that is the first layer of the resulting coating. Proteases together with lipases destroy bacteria by cleaving proteins and lipids, which form a structural component of bacterial cell walls and membranes. Dextranases disrupt the organic backbone structure produced by the bacteria that form a binder for bacterial adhesion. Proteases and amylases not only form coatings, but also prevent the formation of tartar by disrupting the carbohydrate-protein complex that binds calcium, thereby preventing mineralization.

Enzymes suitable for use in the present invention include any commercially available proteases, glucanohydrolase, endoglycosidase, amylase, mutanase, lipase and mucinase, and mixtures thereof. Proteases dextranases, endoglycosidases and mutanases, papain, endoglycosidases and mixtures of dextranase and mutanase are preferred. Other enzymes suitable for use in this invention are disclosed in U.S. Pat. No. 5,000,939 issued to Dring et al. on March 19, 1991, U.S. Pat. No. 4,992,420 issued to Neeser on Feb. 12, 1991; No. 4,355,022 issued to Rabussay on Oct. 19, 1982; No. 4,154,815 issued to Pader on May 15, 1979; No. 4,058,595 issued to Colodney on Nov. 15, 1977; No. 3,991,177 issued to Virda et al. on Nov. 9, 1976; No. 3,696,191, issued to Weeks on Oct. 3, 1972. All of said patents are incorporated herein by reference.

- 148. Products administered by mouth and throat

Other materials used in the present invention include well-known mouth and throat products. These products are listed in "Drug Facts and Comparisons", Wolters Kluer Company, St. Petersburg. Louis, Mo. 1997, p. 520b - 527. These products include, but are not limited to, antifungal agents, antibiotics, and analgesics.

9. Antioxidants

Antioxidants are important in the compositions of the present invention. Antioxidants are disclosed in Cadanes and Packer's "The Handbook of Antioxidants", 1996. Antioxidants included in oral care compositions and substances include, but are not limited to, vitamin E, ascorbic acid, uric acid, carotenoids, vitamin A, flavonoids and polyphenols, herbal antioxidants, melatonin, aminoindoles (lipoic acid), and mixtures thereof.

10. H-2 antagonists (antagonists)

Histamine -2 (H-2 or H) as a receptor antagonist component (H-2 antagonist) can be used in the oral care composition of the present invention. Selected H-2 antagonists are compounds that block H-2 receptors but do not appear to block histamine-1 (H-1 or H) receptors. The selective H-2 antagonist stimulates contractions of the kidney muscles by various organs, for example, the intestines and bronchial tubes, which can be suppressed by a low concentration of mepyramine - a typical antihistamine. The pharmacological receptors involved in these mepyraminosensitive histamine reactions are defined as H-1 receptors (Ash, A.S.F & H.O.Schild, Brit. J. Pharmacol Chemother, Vol. 27 (1966) p. 427). Histamine also stimulates gastric acid secretion (Loew, ER & O. Chickering, Proc.Soc.Exp.Biol.Med., Vol. 48 (1941), p. 65) increases heart rate (Trendelenburg, U., J. Pharmacol, Vol. 1 (1946), p. 278, all references are for comparison), and these actions cannot be antagonized by mepyramine and related substances. H-2 antagonists used in oral care compositions or substances block the receptors involved in the reactions

15-mepyramine-insensitive, non-H-1 (H2) histamine, while not blocking the receptors involved in mepyramine-sensitive histamine reactions.

Optional H-2 antagonists are those compounds known as H-2 antagonists used in classical preclinical assays for H-2 antagonist function. Optional H-2 antagonists are defined as compounds that can be demonstrated as competitive and non-competitive inhibitors of the histamine-mediated phenomenon in screening models that specifically depend on H-2 receptor function, but lack significant histamine antagonist activity for screening models that are dependent on the H1 receptor function. More specifically, they include compounds that can be classified as described in p. Black, J.W., W. A. Duncan, C. R. Ganellin & E.M. Parsons, "Definition and Antagonism of Histamine HReceptors," Nature, vol. 236 (April 21, 1972), p. 385-390 (Black) as an H-2 antagonist when determined as described in p. Black by in vitro testing in guinea pigs that spontaneously pumped the right atrium, and secreted gastric juices in guinea pigs when tested in vivo, showing insufficient H1 antagonist activity compared to H-2 antagonist activity, when tested by the Black method, in guinea pig ileum contraction in in vitro testing, or in abdominal contraction in vivo testing. It is preferred that the selected H-2 antagonist does not show any significant H-1 activity at reasonable dosages in said H-1 assays. A typical appropriate dose is the lowest dose that achieves 90% histamine inhibition, preferably 99% histamine inhibition, in the above H-2 assays.

Optional H-2 antagonists include compounds that meet the criteria set forth in U.S. Pat. Nos. 5,294,433 and 5,364,616 issued to Singer et al. on March 15, 1994 and November 15, 1994, assigned to Co. Procter & Gamble, wherein the H-2 antagonists are selected from the group consisting of cimetidine, etintidine, ranitidine, ICIA-5165, tiotidine, ORF-17578, lupitidine, donetidine, famotidine, roxatidine, pifatidine, lamtidine, BL-6548, BMY 25271, zaltidine, nizatidine, mifentidine, BMY-52368, SKF-94482, BL-6341A, ICI-162846, ramoxitidine, Wy-45727, SR-58042, BMY-25405, loxtidine, DA-4634, bisfentidine, sufotidine, ebrotidine, HE-30-256, D-16637, FRG-8813, FRG-8701, impromidine, L-643728, and HB-408. Especially preferred is cemetidine (SKF-92334),

N-cyano-N'-methyl-N '- (2 - (((5-methyl-1H-imidadol-4-yl) methyl) thio) ethyl) guanidine:

Cimetidine is also disclosed in the Merck Index, 11th Edition (1989) p. 354 (entry 2279) and in the Physicians' Desk Reference, 46th edition (1992) line 2228. Preferred H-2 antagonists include burimainide and metiamide.

As already mentioned, the oral care substance of the present invention may take various forms. However, a gel is preferred, preferably a watery gel. A gel is a matrix material belonging to gel substances known in the art. These gel substances are completely safe when administered orally, do not dissolve readily with saliva and do not react with (or activate) the ingredients in which they are present. Generally, the gelling agent is a swellable polymer. The gel formed by this material provides sufficient adhesion of the film material to the target platform of the oral cavity. The amount of gel material in the gel composition, based on the weight of the composition or substance, is from 0.1% to 15%, preferably from 1% to 10%, more preferably from 2% to 8%, and most preferably from 4% to 6%.

Suitable gelling agents useful in the present invention include carboxypolymetalene, carboxymethyl cellulose, carboxypropyl cellulose, polyoxymers, carrageenan, Veegum, polymers of carboxyvinil and natural gums (gums), for example, karaya gum, xanthan gum, Guar gum, gum arabic, gum tragacanth and gum tragacanth. mixtures thereof. A preferred gel in the present invention is carboxypolymethylene from et al. B. F. Goodrich Company, known under the trademark Carbopol. Of the Carbopols, Carbopol 934, 940, 941, 956 and mixtures thereof are preferred. Carbopol 956 is best suited. Carboxypolymethylene is a slightly acidic vinyl polymer with an active carboxyl group. The usual concentration of carboxypolymethylene resins in water is, according to the manufacturer, below 2%. However, it has been found that a highly viscous gel compound can be prepared in the preparation of supersaturated carboxypolmethylene compounds with an absolute concentration in the above range.

Concentrated carboxypolymethylene gel has, besides high viscosity, many other important properties. Sufficient amount is added to the gel compound

17 carboxypolymethylene, in excess of the amount required to obtain a high viscosity, so that a significant amount of saliva and water is required to reduce the viscosity value and leach the compounds. The concentrated carboxypolymethylene compound also exhibits considerable tackiness and adhesion, by means of which properties the strip of material is firmly attached to the target surface of the oral cavity, especially the teeth. However, care should be taken not to use too much carboxypolymethylene, which may make it difficult to insert and remove a strip of material from the mouth.

If the drug substance is an aqueous gel, the water present in the gel compound should be deionized and free of organic impurities. The water is present in an amount by weight of the substance of from 0.1% to 95%, preferably from 5% to 90%, preferably from 10% to 80%. This amount of water includes the free added water plus the amount contained in other added materials.

The pH-regulating agent is added to optimize the storage stability of the gel and maintain the safety of the substance when applied to the oral tissue. The pH-regulating substance or buffer may be any material that is

Even a substance capable of adjusting the pH. A suitable material may be, for example, baking soda, sodium phosphate, sodium hydroxide, ammonium hydroxide, sodium hexahydroxycinate, tritanolamine, citric acid, hydrochloric acid, sodium citrate, and combinations thereof. The pH-regulating agent is added in a sufficient amount to maintain the pH at a value of from 4.5 to 11, preferably from 5.5 to 8.5, preferably from 6 to 7. The pH-regulating agent is found in a substance in an amount of from 0.01% to 15% by weight of said substance, preferably from 0.05% to 5% by weight of the substance.

Although the described gels provide sufficient adherence, additional gel substances may be added to help the active ingredients adhere to the oral cavity tissue. Soluble materials include both water-insoluble polymers and water-insoluble polymers. These polymers form a thin film on both the soft portions of the oral cavity and on the hard tissues when the saliva is joined to the present composition. Suitable adhesives with limited water solubility may be: hydroxyethyl and propylcellulose. The water-soluble adhesives may be: ethylcellulose and polyoxin resin. Another suitable adhesive for use in the composition is polyvinylpyrrolidone

- 18 with a molecular weight of about 50,000 to 300,000. Another suitable adhesive is a combination of Gantrez and a semisynthetic, water-soluble carboxymethylcellulose polymer.

Additional carrier material may be added to the oral care substance. The carrier material may be humectants. Suitable humectants may be glycerin, sorbitol, polyethylene glycol propylene glycol, and other polyhydric alcohols. Humectants are generally present in an amount of from 10% to 95%, preferably from 50% to 80% by weight of the substance or composition. In addition to the gel materials of the present invention, other ingredients may be added to the substance. These other ingredients include, but are not limited to, flavoring agents, sweeteners, xylitol, opacifiers, colorants, and chelants, for example, ethylenediaminetetraacetic acid. These additional components may replace the above compounds.

Removable washer

The removable mat may be formed from any material that exhibits less affinity for the oral care substance than the substance itself and the strip of material. The removable backing comprises a rigid sheet of material, such as polyethylene, paper, polyester, and other material, which is subsequently coated with a non-stick material. The release liner may be coated with wax, silicone, teflon, fluorine polymers and other non-stick material. A preferred release liner is Schotchpack, manufactured by Co. 3M. The release liner is cut to the same size and shape as the strip of material, or it can be cut into larger pieces than the size of the strip of material to provide an easily accessible means of separating the material from the strip. The removable backing may be formed of a brittle material that breaks upon bending, or may be formed of several pieces of material, or a material having grooves. Alternatively, the insert may be made of two superposed pieces, as is the case with typical bandage adhesive strips. For a further description of suitable release liner materials, see Kirk-Othmer Encyclopedia of Chemical Technology, Fourth Edition, Volume 21, p. 207-218. This document is included for comparison.

- 19Examples

The strip of material J2 is a 0.013 mm thick polyethylene film. The film is provided with a set of shallow buckets, 0.4 mm wide and 0.1 mm deep. The strip of material 12 has a flexural stiffness of about 0.6 g / cm, as measured on a Handle-O-Meter, model # 211-300, available from Co. Thwing-Albert Instrument Co. of Philadelphia, PA, using the ASTM D2923-95 Test Method.

An example of a tooth whitening agent is a gel, described as follows: Combine 70% glycerin, 5% carboxypolymethylene, 10% carmabide peroxide, 15% acidified pH 6.5 with sodium hydroxide. Stir until the mixture is homogeneous. The delivery system of the present invention also utilizes Opalescence Bleach and Nu-Pro Gold.

An example of a gel composition for oral care according to the present invention includes an H-2 antagonist made by a routine method and comprising a mixture of 2.50% hydroxyethyl cellulose, 0.09% sodium fluoride, 0.05% sodium saccharide, 00% ranitidine and pure water.

An exemplary composition according to the invention comprises enzymes produced routinely and comprising 61.814% sorbitol, 0.314% carbopol, 0.534% xantham gum, 1.132% citric acid, 6.291% sodium citrate, 5.033% sodium lauroyl sarcosinate (30% solution) ), 7.864% endoglycosidase (3.2% solution), 0.305% sodium fluoride, and water.

Method of use

In practicing the present invention, a strip of material is applied to a designated surface of the user's oral cavity. The side of the material facing the oral cavity surface is coated with the drug substance in a high viscous state.

The drug substance is a carrier of the active agent and of the adhesive, which serves to adhere the strip of material to the surface of the oral cavity, where the strip of material must withstand a specified period of time. If the active substance is other than a bleaching agent, the designated time is from one minute to 30 minutes. For an active substance that requires a longer diffusion time into the surface of the oral cavity, such as a bleach, the strip of material is used over time,

-20 necessary to deliver the active agent at a dosage necessary to meet the stated goal. It may take half an hour or even several hours.

The strip of material adheres easily to the surface of the oral cavity by lightly pressing. The strip of material is easily removed by peeling or peeling off the surface of the oral cavity. Each additional treatment requires a new strip of material. If the oral cavity surface is a tooth, no preparation of the tooth surface is required prior to application of the system of the invention. This means that the user does not need to use a toothbrush or rinse his mouth before applying the strip. The tooth surface does not need to be dried or moistened with saliva or water.

It is preferred that the strip of drug substance material is transparent and not visible during use. The thinness of the strip of material may also increase the surface temperature of the oral cavity, thereby accelerating the diffusion of the active material into the surface of the oral cavity.

If the user removes the strip of material from the oral cavity surface, the remainder of the drug substance may remain on the surface. This remainder of the drug substance will not be great at all, since the substance exhibits affinity for both the film and itself. The remainder of the substance can be easily removed by rubbing, using a toothbrush and rinsing the oral cavity.

While a particular embodiment of the invention has been described, it will be apparent to those skilled in the art that various changes and modifications may be made within the scope of the invention, which are within the scope of the present invention to cover the appended claims.

Claims (8)

PATENT CLAIMS First A delivery system for delivering a whitening substance to the oral cavity, the delivery system comprising: while (a) a strip of resilient material with sufficient resiliency to produce a curved shape on the surface of the oral cavity, said strip of material having a substantially constant bending stiffness of less than 5g / cm, measured on a Handle-O-Meter using ASTM Test Method D2923- 95, wherein said strip of material is compatible with the drug substance of the oral cavity and is impervious to liquids, preferably made of polyethylene while being adaptable to the oral cavity surface without permanent deformation upon introduction into the oral cavity, preferably in order for said strip of material to be able to return to its deformed state in the absence of adhesion force due to said therapeutic substance, further comprising a therapeutic substance, preferably a gel which is applied to the strip of material in the form of a continuous coating which placed on set instead of on the surface of the oral cavity, the substance contacts the surface and imparts the active substance to said surface, wherein the drug substance also provides an adhesive connection between said strip of material and said surface, ensuring that the delivery system is maintained in place for a specified period of time to allow the active substance to act on said surface. A delivery system according to claim 1, characterized in that the active substance in said drug substance is selected from the group consisting of active tooth whitening agents, phosphates, fluoride ion sources, antimicrobials, anti-inflammatory agents, nutrients, enzymes, products , mouth and throat, antioxidants, H-2 antagonists, and mixtures thereof. -223. A delivery system according to claim 1 and 2, characterized in that said strip of drug substance deposited has a total thickness of less than 1 mm, preferably having a nominal thickness of less than 0.1 mm, preferably if said strip of drug substance does not use by another person. A delivery system according to claims 1, 2 and 3, characterized in that the force required to peel the strip of material with the substance is less than 50 g, preferably if the force required is such that no tool is required to remove the strip from the oral cavity. , no chemical solvent and excessive frictional force. A delivery system according to claim 1 to 4, characterized in that the delivery system is applied to the tissue of the surrounding teeth and to the surface of the teeth in such a way that the surface of the teeth does not have to be treated before application. A delivery system according to claim 1 to 5, wherein said strip of material comprises shallow buckets on the side coated with the drug substance, said shallow buckets containing said drug substance. The delivery system of claims 1 to 6, wherein said drug substance comprises carboxypolmethylene having a value of from 0.5% to 12% by weight of the drug substance. The delivery system of claim 1 to 7, wherein said drug substance comprises water in an amount of from 0.1% to 95% by weight of said drug substance. The delivery system of claims 1-8, further comprising a release pad. 10. A method of administering a drug substance to a tooth surface comprises the following steps: a) applying said substance to said strip of material having sufficient flexibility to form a curved shape on the surface of the oral cavity, said strip of material having a substantially constant bending stiffness of less than 5g / cm, measured on a Handle-O-Meter by the ASTM test method D2923-95, wherein said strip of material is compatible with the drug substance of the oral cavity and is impervious to liquids, preferably being made of polyethylene while being adaptable to the oral cavity surface without permanent deformation upon introduction into the oral cavity a cavity, it being preferred that said strip of material be able to return from a deformed state to its original state in the absence of adhesion force due to said drug substance, b) applying said strip of material to the drug substance, the accuracy being given to a gel which is applied to the strip of material in the form of a continuous coating, which causes, that after being placed at a predetermined surface of the oral cavity surface, the substance contacts the surface and imparts the active agent to said surface, wherein the drug substance also provides an adhesive connection between said strip of material and said surface, allowing the active ingredient to act on said surface.